288 research outputs found
N-Acyl Homoserine Lactones and Lux Solos Regulate Social Behaviour and Virulence of Pseudomonas syringae pv. actinidiae
The phyllosphere is a complex environment where microbes communicate through signalling molecules in a system, generally known as quorum sensing (QS). One of the most common QS systems in Gram-negative proteobacteria is based on the production of N-acyl homoserine lactones (AHLs) by a LuxI synthase and their perception by a LuxR sensor. Pseudomonas syringae pv. actinidiae (Psa), the aetiological agent of the bacterial canker of kiwifruit, colonises plant phyllosphere before penetrating via wounds and natural openings. Since Psa genome encodes three LuxR solos without a cognate LuxI, this bacterium may perceive diffusible signals, but it cannot produce AHLs, displaying a non-canonical QS system. The elucidation of the mechanisms underlying the perception of environmental cues in the phyllosphere by this pathogen and their influence on the onset of pathogenesis are of crucial importance for a long-lasting and sustainable management of the bacterial canker of kiwifruit. Here, we report the ability of Psa to sense its own population density and the presence of surrounding bacteria. Moreover, we show that Psa can perceive AHLs, indicating that AHL-producing neighbouring bacteria may regulate Psa virulence in the host. Our results suggest that the ecological environment is important in determining Psa fitness and pathogenic potential. This opens new perspectives in the use of more advanced biochemical and microbiological tools for the control of bacterial canker of kiwifruit
Comparative transcriptome analysis of the interaction between Actinidia chinensis var. chinensis and Pseudomonas syringae pv. Actinidiae in absence and presence of acibenzolar-S-methyl
Background: Since 2007, bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) has become a pandemic disease leading to important economic losses in every country where kiwifruit is widely cultivated. Options for controlling this disease are very limited and rely primarily on the use of bactericidal compounds, such as copper, and resistance inducers. Among the latter, the most widely studied is acibenzolar-S-methyl. To elucidate the early molecular reaction of kiwifruit plants (Actinidia chinensis var. chinensis) to Psa infection and acibenzolar-S-methyl treatment, a RNA seq analysis was performed at different phases of the infection process, from the epiphytic phase to the endophytic invasion on acibenzolar-S-methyl treated and on non-treated plants. The infection process was monitored in vivo by confocal laser scanning microscopy. Results: De novo assembly of kiwifruit transcriptome revealed a total of 39,607 transcripts, of which 3360 were differentially expressed during the infection process, primarily 3 h post inoculation. The study revealed the coordinated changes of important gene functional categories such as signaling, hormonal balance and transcriptional regulation. Among the transcription factor families, AP2/ERF, MYB, Myc, bHLH, GATA, NAC, WRKY and GRAS were found differentially expressed in response to Psa infection and acibenzolar-S-methyl treatment. Finally, in plants treated with acibenzolar-S-methyl, a number of gene functions related to plant resistance, such as PR proteins, were modulated, suggesting the set-up of a more effective defense response against the pathogen. Weighted-gene coexpression network analysis confirmed these results. Conclusions: Our work provides an in-depth description of the plant molecular reactions to Psa, it highlights the metabolic pathway related to acibenzolar-S-methyl-induced resistance and it contributes to the development of effective control strategies in open field
Transitions between Inherent Structures in Water
The energy landscape approach has been useful to help understand the dynamic
properties of supercooled liquids and the connection between these properties
and thermodynamics. The analysis in numerical models of the inherent structure
(IS) trajectories -- the set of local minima visited by the liquid -- offers
the possibility of filtering out the vibrational component of the motion of the
system on the potential energy surface and thereby resolving the slow
structural component more efficiently. Here we report an analysis of an IS
trajectory for a widely-studied water model, focusing on the changes in
hydrogen bond connectivity that give rise to many IS separated by relatively
small energy barriers. We find that while the system \emph{travels} through
these IS, the structure of the bond network continuously modifies, exchanging
linear bonds for bifurcated bonds and usually reversing the exchange to return
to nearly the same initial configuration. For the 216 molecule system we
investigate, the time scale of these transitions is as small as the simulation
time scale ( fs). Hence for water, the transitions between each of
these IS is relatively small and eventual relaxation of the system occurs only
by many of these transitions. We find that during IS changes, the molecules
with the greatest displacements move in small ``clusters'' of 1-10 molecules
with displacements of nm, not unlike simpler liquids.
However, for water these clusters appear to be somewhat more branched than the
linear ``string-like'' clusters formed in a supercooled Lennar d-Jones system
found by Glotzer and her collaborators.Comment: accepted in PR
Personalized rTMS for Depression: A Review
Personalized treatments are gaining momentum across all fields of medicine.
Precision medicine can be applied to neuromodulatory techniques, where focused
brain stimulation treatments such as repetitive transcranial magnetic
stimulation (rTMS) are used to modulate brain circuits and alleviate clinical
symptoms. rTMS is well-tolerated and clinically effective for
treatment-resistant depression (TRD) and other neuropsychiatric disorders.
However, despite its wide stimulation parameter space (location, angle,
pattern, frequency, and intensity can be adjusted), rTMS is currently applied
in a one-size-fits-all manner, potentially contributing to its suboptimal
clinical response (~50%). In this review, we examine components of rTMS that
can be optimized to account for inter-individual variability in neural function
and anatomy. We discuss current treatment options for TRD, the neural
mechanisms thought to underlie treatment, differences in FDA-cleared devices,
targeting strategies, stimulation parameter selection, and adaptive closed-loop
rTMS to improve treatment outcomes. We suggest that better understanding of the
wide and modifiable parameter space of rTMS will greatly improve clinical
outcome
Dynamics in a supercooled molecular liquid: Theory and Simulations
We report extensive simulations of liquid supercooled states for a simple
three-sites molecular model, introduced by Lewis and Wahnstr"om [L. J. Lewis
and G. Wahnstr"om, Phys. Rev. E 50, 3865 (1994)] to mimic the behavior of
ortho-terphenyl. The large system size and the long simulation length allow to
calculate very precisely --- in a large q-vector range --- self and collective
correlation functions, providing a clean and simple reference model for
theoretical descriptions of molecular liquids in supercooled states. The time
and wavevector dependence of the site-site correlation functions are compared
with detailed predictions based on ideal mode-coupling theory, neglecting the
molecular constraints. Except for the wavevector region where the dynamics is
controlled by the center of mass (around 9 nm-1), the theoretical predictions
compare very well with the simulation data.
Equilibration times in numerical simulation of structural glasses: Comparing parallel tempering and conventional molecular dynamics
Generation of equilibrium configurations is the major obstacle for numerical
investigation of the slow dynamics in supercooled liquid states. The parallel
tempering (PT) technique, originally proposed for the numerical equilibration
of discrete spin-glass model configurations, has recently been applied in the
study of supercooled structural glasses. We present an investigation of the
ability of parallel tempering to properly sample the liquid configuration space
at different temperatures, by mapping the PT dynamics into the dynamics of the
closest local potential energy minima (inherent structures). Comparing the PT
equilibration process with the standard molecular dynamics equilibration
process we find that the PT does not increase the speed of equilibration of the
(slow) configurational degrees of freedom.Comment: 5 pages, 3 figure
Rare Pathogenic Variants Predispose to Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is a rising cause of hepatocellular carcinoma (HCC). We examined whether inherited pathogenic variants in candidate genes (n = 181) were enriched in patients with NAFLD-HCC. To this end, we resequenced peripheral blood DNA of 142 NAFLD-HCC, 59 NAFLD with advanced fibrosis, and 50 controls, and considered 404 healthy individuals from 1000 G. Pathogenic variants were defined according to ClinVar, likely pathogenic as rare variants predicted to alter protein activity. In NAFLD-HCC patients, we detected an enrichment in pathogenic (p = 0.024), and likely pathogenic variants (p = 1.9*10 126 ), particularly in APOB (p = 0.047). APOB variants were associated with lower circulating triglycerides and higher HDL cholesterol (p < 0.01). A genetic risk score predicted NAFLD-HCC (OR 4.96, 3.29\u20137.55; p = 5.1*10 1216 ), outperforming the diagnostic accuracy of common genetic risk variants, and of clinical risk factors (p < 0.05). In conclusion, rare pathogenic variants in genes involved in liver disease and cancer predisposition are associated with NAFLD-HCC development
Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study
Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients
Inflammatory Adipokines, High Molecular Weight Adiponectin, and Insulin Resistance: A Population-Based Survey in Prepubertal Schoolchildren
BackgroundThe aim of this study was to investigate sex differences and associations of high molecular weight (HMW) adiponectin, leptin and proinflammatory adipokines, individually or in combinations, with adiposity and insulin resistance (IR) measures in prepubertal childhood.MethodologyWe studied 305 prepubertal children (boys/girls: 144/161; Tanner stage 1; age: 5-13 yr), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole's criteria, 105 individuals were lean (L; boys/girls: 59/46), 60 overweight (OW; boys/girls: 32/28) and 140 obese (OB; boys/girls: 70/70). Measurements comprised total and HMW adiponectin, leptin, as well as a panel of proinflammatory adipokines/chemokines associated with diabetes risk.Principal findingsLeptin-, and the leptin-to-HMW adiponectin ratio (L/HMW)-, increased progressively (pConclusionsIn prepubertal children, leptin emerges as a sex-independent discrimination marker of adiposity degree and as a useful, sex-associated predictor of the systemic insulin resistance
- …